Identification of macrodomain proteins as novel O-acetyl-ADP-ribose deacetylases.
Sirtuins are a family of protein lysine deacetylases, which regulate gene silencing, metabolism, life span, and chromatin structure. Sirtuins utilize NAD(+) to deacetylate proteins, yielding O-acetyl-ADP-ribose (OAADPr) as a reaction product. The macrodomain is a ubiquitous protein module known to b...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2011
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| _version_ | 1797069734895681536 |
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| author | Chen, D Vollmar, M Rossi, M Phillips, C Kraehenbuehl, R Slade, D Mehrotra, P von Delft, F Crosthwaite, S Gileadi, O Denu, J Ahel, I |
| author_facet | Chen, D Vollmar, M Rossi, M Phillips, C Kraehenbuehl, R Slade, D Mehrotra, P von Delft, F Crosthwaite, S Gileadi, O Denu, J Ahel, I |
| author_sort | Chen, D |
| collection | OXFORD |
| description | Sirtuins are a family of protein lysine deacetylases, which regulate gene silencing, metabolism, life span, and chromatin structure. Sirtuins utilize NAD(+) to deacetylate proteins, yielding O-acetyl-ADP-ribose (OAADPr) as a reaction product. The macrodomain is a ubiquitous protein module known to bind ADP-ribose derivatives, which diverged through evolution to support many different protein functions and pathways. The observation that some sirtuins and macrodomains are physically linked as fusion proteins or genetically coupled through the same operon, provided a clue that their functions might be connected. Indeed, here we demonstrate that the product of the sirtuin reaction OAADPr is a substrate for several related macrodomain proteins: human MacroD1, human MacroD2, Escherichia coli YmdB, and the sirtuin-linked MacroD-like protein from Staphylococcus aureus. In addition, we show that the cell extracts derived from MacroD-deficient Neurospora crassa strain exhibit a major reduction in the ability to hydrolyze OAADPr. Our data support a novel function of macrodomains as OAADPr deacetylases and potential in vivo regulators of cellular OAADPr produced by NAD(+)-dependent deacetylation. |
| first_indexed | 2024-03-06T22:28:50Z |
| format | Journal article |
| id | oxford-uuid:579990d1-6175-4613-a156-d48f4cda7cac |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:28:50Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:579990d1-6175-4613-a156-d48f4cda7cac2022-03-26T16:57:40ZIdentification of macrodomain proteins as novel O-acetyl-ADP-ribose deacetylases.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:579990d1-6175-4613-a156-d48f4cda7cacEscherichia coli ProteinsEscherichia coliStaphylococcus aureuschemistryProtein Structure, TertiarySirtuinsFungal ProteinsgeneticsHumansNeurospora crassaenzymologyEvolution, MolecularmetabolismHela CellsEnglishStructural Genomics Consortium2011Chen, DVollmar, MRossi, MPhillips, CKraehenbuehl, RSlade, DMehrotra, Pvon Delft, FCrosthwaite, SGileadi, ODenu, JAhel, ISirtuins are a family of protein lysine deacetylases, which regulate gene silencing, metabolism, life span, and chromatin structure. Sirtuins utilize NAD(+) to deacetylate proteins, yielding O-acetyl-ADP-ribose (OAADPr) as a reaction product. The macrodomain is a ubiquitous protein module known to bind ADP-ribose derivatives, which diverged through evolution to support many different protein functions and pathways. The observation that some sirtuins and macrodomains are physically linked as fusion proteins or genetically coupled through the same operon, provided a clue that their functions might be connected. Indeed, here we demonstrate that the product of the sirtuin reaction OAADPr is a substrate for several related macrodomain proteins: human MacroD1, human MacroD2, Escherichia coli YmdB, and the sirtuin-linked MacroD-like protein from Staphylococcus aureus. In addition, we show that the cell extracts derived from MacroD-deficient Neurospora crassa strain exhibit a major reduction in the ability to hydrolyze OAADPr. Our data support a novel function of macrodomains as OAADPr deacetylases and potential in vivo regulators of cellular OAADPr produced by NAD(+)-dependent deacetylation. |
| spellingShingle | Escherichia coli Proteins Escherichia coli Staphylococcus aureus chemistry Protein Structure, Tertiary Sirtuins Fungal Proteins genetics Humans Neurospora crassa enzymology Evolution, Molecular metabolism Hela Cells Chen, D Vollmar, M Rossi, M Phillips, C Kraehenbuehl, R Slade, D Mehrotra, P von Delft, F Crosthwaite, S Gileadi, O Denu, J Ahel, I Identification of macrodomain proteins as novel O-acetyl-ADP-ribose deacetylases. |
| title | Identification of macrodomain proteins as novel O-acetyl-ADP-ribose deacetylases. |
| title_full | Identification of macrodomain proteins as novel O-acetyl-ADP-ribose deacetylases. |
| title_fullStr | Identification of macrodomain proteins as novel O-acetyl-ADP-ribose deacetylases. |
| title_full_unstemmed | Identification of macrodomain proteins as novel O-acetyl-ADP-ribose deacetylases. |
| title_short | Identification of macrodomain proteins as novel O-acetyl-ADP-ribose deacetylases. |
| title_sort | identification of macrodomain proteins as novel o acetyl adp ribose deacetylases |
| topic | Escherichia coli Proteins Escherichia coli Staphylococcus aureus chemistry Protein Structure, Tertiary Sirtuins Fungal Proteins genetics Humans Neurospora crassa enzymology Evolution, Molecular metabolism Hela Cells |
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